Ever present hurdles for the discovery of new drugs for cancer therapy have necessitated the development of the alternative strategy of drug repurposing, the development of old drugs for new therapeutic purposes. This strategy with a cost-effective way offers a rare opportunity for the treatment of human neoplastic disease, facilitating rapid clinical translation. With an increased understanding of the hallmarks of cancer and the development of various data-driven approaches, drug repurposing further promotes the holistic productivity of drug discovery and reasonably focuses on target-defined antineoplastic compounds. The “treasure trove” of non-oncology drugs should not be ignored since they could target not only known but also hitherto unknown vulnerabilities of cancer. Indeed, different from targeted drugs, these old generic drugs, usually used in a multi-target strategy may bring benefit to patients. In this review, aiming to demonstrate the full potential of drug repurposing, we present various promising repurposed non-oncology drugs for clinical cancer management and classify these candidates into their proposed administration for either mono- or drug combination therapy. We also summarize approaches used for drug repurposing and discuss the main barriers to its uptake.

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Overcoming cancer therapeutic bottleneck by drug repurposing

Inorganic nanocrystals have attracted much attention for therapeutic and diagnostic applications due to their unique optical, magnetic, and fluorescent properties.[1] Among these various nanocrystals, colloidal superparamagnetic iron oxide (e.g., γ-Fe2O3 and Fe3O4) have been extensively highlighted for many biomedical applications such as contrast agents for magnetic-resonance (MR) imaging, therapeutic gene carriers, protein purification, and sensors for nucleic-acid and virus detection.[2] In principle, it is of utmost importance to prepare highly stable magnetic nanocrystals in aqueous solutions to maximize in vivo half-life and tissue-specificity. However, the fabrication of such stable, bioactive magnetic nanocolloids has proven to be nontrivial.

Bio-inspired Surface Imobilization of Hyaluronic Acid on Mondisperse Magnetic Nano-crystals for Targeted Cancer Imaging

Covalent adaptable networks (CANs), unlike typical thermosets or other covalently crosslinked networks, possess a unique, often dormant ability to activate one or more forms of stimuli-responsive, dynamic covalent chemistries as a means to transition their behavior from that of a viscoelastic solid to a material with fluid-like plastic flow. Upon application of a stimulus, such as light or other irradiation, temperature, or even a distinct chemical signal, the CAN responds by transforming to a state of temporal plasticity through activation of either reversible addition or reversible bond exchange, either of which allows the material to essentially re-equilibrate to an altered set of conditions that are distinct from those in which the original covalently crosslinked network is formed, often simultaneously enabling a new and distinct shape, function, and characteristics. As such, CANs span the divide between thermosets and thermoplastics, thus offering unprecedented possibilities for innovation in polymer and materials science. Without attempting to comprehensively review the literature, recent developments in CANs are discussed here with an emphasis on the most effective dynamic chemistries that render these materials to be stimuli responsive, enabling features that make CANs more broadly applicable.

Toward Stimuli-Responsive Dynamic Thermosets through Continuous Development and Improvements in Covalent Adaptable Networks (CANs)

Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric (Curcuma longa). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants (e.g., Coptis chinensis) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

5353 The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumor formation in nude mice. The constitutive activation of Stat3 has been frequently detected in various types of human cancers. However, the constitutive activation of Stat3 in endometrial and cervical cancers has not been studied. We examined tyrosine phosphorylation of Stat3 (activated form of Stat3) in multiple endometrial and cervical cancer tissues using tissue microarray slides as well as cancer cell lines to explore the possible activation of Stat3. Our results indicated that elevated phosphorylation of Stat3 was detected in cervical and endometrial cancer cell lines. Our results also showed that elevated levels of phosphorylation of Stat3 protein were detected in the endometrial and cervical cancer specimens. This is the first study to demonstrate that Stat3 is activated in human endometrial and cervical cancer tissues. Immunohistochemical staining showed that activated Stat3 is associated with increased expression of down stream antiapoptotic genes, Bcl-xL, survivin, and Mcl-1 in these tissues. Expression of a dominant-negative Stat3 mutant using adenovirus-mediated gene transfer inhibited cell growth and induced apoptosis in Hela and SiHa cervical cancer cell lines expressing elevated levels of Stat3 phosphorylation. Further, a JAK/Stat3 small molecular inhibitor, JSI-124, induced apoptosis more selectively in Hela and SiHa cancer cell lines than Ishikawa cell line without elevated levels of Stat3 phosphorylation. These results indicate that Stat3 is activated in human endometrial and cervical cancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers.

Stat3 activation in human endometrial and cervical cancers

Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2.

Nanocomposite hydrogel with NIR/magnet/enzyme multiple responsiveness to accurately manipulate local drugs for on-demand tumor therapy.

Hepatocellular carcinoma (HCC) is a biologically complex disease. Combination chemotherapy is a good strategy after surgery treatment. In this study, we report that berberine combined with HMQ1611 (BCH) had a good synergistic effect on the HCC. Our findings concluded that BCH showed good inhibition on the HCC proliferation and colony formation, which attributed to cell cycle arrest by BCH at G1 phase through impairing the expression of cyclinD1, cyclinE, and cdc2 and downregulated the phosphorylation of Akt, mTOR, and ERK. Moreover, BCH negatively regulated Wnt signaling pathway by upregulating the Axin and inhibiting the nuclear translocation of β-catenin. BCH suppressed the phosphorylation of LRP5/6, GSK3β, the expression of Wnt5a, Frizzled8, CK1, and APC, as well as the nucleus protein included MMP2, MMP3, MMP9, and c-myc. The above data of Wnt signaling regulators contributed to inhibition by BCH on cell migration. In vivo studies, BCH significantly suppressed the growth of SMMC-7721 xenograft tumors through downregulating Ki67 and β-catenin, as well as upregulating Axin and p-β-catenin. In conclusion, the results revealed that BCH exhibited potential antitumor activities against human liver cancer in vitro and in vivo, and the potential mechanism underlying these activities depended on the inhibition of the Wnt/β-catenin signaling pathway.

Synergistic effect of berberine and HMQ1611 impairs cell proliferation and migration by regulating Wnt signaling pathway in hepatocellular carcinoma.

This paper presents a method for the preparation of a graphene-based hybrid composite film by electrodeposition of reduced graphene oxide and overoxidized electropolymerized polypyrrole onto a glassy carbon electrode (GCE) using cyclic voltammetry. The morphology of the hybrid composite film was characterized by scanning electron microscopy. The electrochemical activity of the modified GCE was studied by cyclic voltammetry using the negatively charged redox probe Fe(CN)63− and the positively charged redox probe Ru(NH3)63+. The modified GCE displays excellent electrocatalytic activity for dopamine (DA) and uric acid (UA), but electrostatically repulses ascorbate anion under physiological pH conditions. The voltammetric response to DA is linear in the 2.0 μM to 160 μM concentration range even in the presence of 1.0 mM ascorbic acid and 0.1 mM of UA. The detection limit is 0.5 μM. The amperometric response to DA (best measured at 0.22 V vs. Ag/AgCl) extends from 0.4 μM to 517 μM and has a 0.2 μM detection limit.

Preparation of a glassy carbon electrode modified with reduced graphene oxide and overoxidized electropolymerized polypyrrole, and its application to the determination of dopamine in the presence of ascorbic acid and uric acid

Tianfeng Yang

Papers

Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2.

Nanocomposite hydrogel with NIR/magnet/enzyme multiple responsiveness to accurately manipulate local drugs for on-demand tumor therapy.

Synergistic effect of berberine and HMQ1611 impairs cell proliferation and migration by regulating Wnt signaling pathway in hepatocellular carcinoma.

Preparation of a glassy carbon electrode modified with reduced graphene oxide and overoxidized electropolymerized polypyrrole, and its application to the determination of dopamine in the presence of ascorbic acid and uric acid

Cyanostilbene-based near-infrared emissive platinum(II) metallacycles for cancer theranostics